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Characterization of the Tetraspanin protein Tspan18

Colombo, Dario (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Tetraspanins are a superfamily of four-transmembrane proteins. They associate laterally with one another and with other transmembrane proteins to form membrane microdomains, in which associated proteins are regulated. Tetraspanins regulate diverse processes such as cell signalling and fusion, intracellular trafficking, viral infection and cancer. The primary aim of this thesis was to study a previously uncharacterized tetraspanin, Tspan18. Unlike other tetraspanins, over-expression of Tspan18 in lymphocyte cell lines activated an NFAT/AP-1 reporter, which responds to calcium and MAPK signalling. In DT40 B cell lines, Tspan18 signalling was independent of Lyn, Syk, PLC2 and IP3 receptors, which are essential for B cell receptor signalling. However, Tspan18 signalling did require extracellular calcium and the calcium-activated phosphatase calcineurin, which activates NFAT. Additional studies that included the Jurkat T cell line showed that Tspan18 could not activate the MAPK-responsive AP-1 promoter, but instead mimicked the effect of the calcium ionophore ionomycin. For the secondary thesis aim, over-expression of Tspan18 or other tetraspanins did not affect signalling by the platelet collagen receptor GPVI. Finally, Tspan18 mRNA was found to be relatively highly expressed in endothelial cells and peripheral blood leukocytes. Together these data suggest a role for Tspan18 in calcium signalling on these cell types.

Type of Work:Ph.D. thesis.
Supervisor(s):Tomlinson, Michael G and Watson, Steve P
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Department of Cardiovascular Sciences
Keywords:Tetraspanin
Subjects:Q Science (General)
R Medicine (General)
Institution:University of Birmingham
ID Code:983
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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